Carbamic acid, ethyl ester → Glycidyl cholesterol

HRID 216994

Reaction equation

HRID 216994 reaction equation
[CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].N[C:30]([O:32][CH2:33][CH3:34])=O.CC(C)([O-])C.[Li+].C(C1OC1)Br>CC(N(C)C)=O>[CH2:34]([CH2:3][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:1])[CH:33]1[O:32][CH2:30]1

Participants

6

Reactant 4

HCID 5641Carbamic acid, ethyl esterHCID 5997Cholesterol2×HCID 18430EpibromohydrinHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

Product 1

HCID 86601307Glycidyl cholesterol

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
5 °C

Procedure

A schematic diagram of the reactions used for covalent binding of cholesterol to the urethane hard segments by the reaction of bromobutylated Tecothane® with 2-hydroxy-3-β-cholesteryloxypropanethiol is presented in FIGS. 1 and 2. Glycidyl cholesterol (FIG. 1) was synthesized by dissolving cholesterol in DMAc under a flow of dry argon and adding 1 M lithium tert-butoxide in hexanes. After cooling to 5° C., freshly distilled epibromohydrin was added and the mixture was stirred at 3-5° C. for 2 hours and allowed to slowly come to room temperature (21-23° C.) where it was incubated for an additional hour. The reaction mixture was diluted with 0.5% aqueous KHCO3 and extracted with three administrations of n-heptane. The combined organic layers were dried over Na2SO4. After filtration from the desiccant, the solvent was removed in vacuo and the residue was purified by flash-chromatography on silica gel employing elution with hexane, hexane/toluene (1:1 mixture), and toluene. The fractions containing pure glycidyl cholesterol were pooled and dried in vacuo until crystallization occurred. Purity was confirmed with 1H NMR (data not shown).

Workup

  1. customto slowly come to room temperature
  2. custom(21-23° C.) where it
  3. waitwas incubated for an additional hour
  4. extractionextracted with three administrations of n-heptane
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationAfter filtration from the desiccant
  7. customthe solvent was removed in vacuo
  8. customthe residue was purified by flash-chromatography on silica gel employing elution with hexane, hexane/toluene (1:1 mixture), and toluene
  9. additionThe fractions containing pure glycidyl cholesterol
  10. customdried in vacuo until crystallization

Sources & evidence

ORD record
ord-b925f5e4396e4cdabe392ee919cb813f
Source dataset
uspto-grants-2012_06
Patent number
US08193290B2

Linked notes

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